Effects of octopamine on lipolysis, glucose transport and amine oxidation in mammalian fat cells

Octopamine is known to exert adrenergic effects in mammals although specifi c octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells tranfected with human alpha(2)-ARs. More recently, we reported that octopamine stimulates lipolysis through beta(3)-rather than b eta(1)-or beta(2)-AR activation in white adipocytes From different mammalia n species. The present study was thus undertaken to further characterize th e adrenergic properties of octopamine. For this purpose, several biological processes known to be regulated by adrenergic stimulation were studied in response to octopamine, noradrenaline, adrenaline and tyramine in white adi pocytes from different mammals. First, octopamine was fully lipolytic in ga rden dormouse and Siberian hamster while tyramine was ineffective. Although being around one hundred-fold less potent that noradrenaline, octopamine w as slightly more potent in these hibernators known for their high sensitivi ty to beta(3)-AR agonists than in rat and chiefly more active than in human adipocytes known for their limited responses to beta(3)-AR agonists. Secon d, octopamine reduced insulin-dependent glucose transport in rat fat cells, a response also observed with noradrenaline and selective beta(3)-AR agoni sts but not with beta(1)-or beta(2)-agonists. Third, human adipocytes, whic h endogenously express a high level of alpha(2)-ARs, exhibited a clear alph a(2)-adrenergic antilipolytic response to adrenaline but not to octopamine. Moreover, octopamine exhibited only a very weak affinity for the alpha(2A) -ARs labeled by [H-3]RX821002 in human adipocyte membranes. In Syrian hamst er adipocytes, which also possess alpha(2)-ARs, octopamine induced only a w eak antilipolysis. Finally, octopamine was a substrate of fat cell amine ox idases, with an apparent affinity similar to that of noradrenaline. All the se results demonstrate that octopamine, tyramine noradrenaline and adrenali ne can be degraded by adipocyte amine oxidases. However these biogenic amin es interact differently with adipocyte adrenoceptors: tyramine is inactive, adrenaline and noradrenaline activate both beta- and alpha(2)-ARs while oc topamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic ag onism. Thus, octopamine could be considered as an endogenous selective beta (3)-AR agonist. (C) 2000 Elsevier Science Inc. All rights reserved.